Many insulin-dependent diabetic (IDDM) adolescents have elevated growth hormone (GH) and low insulin-like growth factor-I (IGF-I) levels, which may contribute to insulin-resistance and further exacerbate already compromised mechanisms of fuel homeostasis. This study compared baseline IGF system parameters and responses to exogenous IGF-I in normal and IDDM male adolescents. Subjects were studied before and after daily 10 hour subcutaneous infusions of saline or IGF-I (20 microg/kg/hour). Baseline overnight GH secretion and IGFBP1 and 3 levels were not significantly different, but IGF-I levels were lower and IGF-II levels were higher in diabetics compared to controls. IGF-I infusion produced an increase of 3-4 fold in serum IGF-I levels and a profound reduction in IGF-II levels. IGFBP1 levels increased dramatically in diabetics and modestly in normals during two days of IGF-I infusion but IGFBP3 levels were not affected. Spontaneous overnight and arginine-stimulated GH secretion were suppressed by approximately 50% in both groups following IGF-I infusion. Insulin requirements were substantially reduced in diabetics receiving IGF-I and insulin secretion was suppressed in normals, with no evidence of a change in insulin half-life. No hypoglycemia or other adverse effect occurred during IGF-I infusions. Longer-terms trials of combined insulin/IGF-I therapy will be necessary to determine if a more physiological increase in IGF-I and normalization of GH levels can safely achieve better metabolic and anabolic balance in the treatment of IDDM in adolescents.